200,390 results match your criteria Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees[Journal]


Structures of fungal and plant acetohydroxyacid synthases.

Nature 2020 Jul 8. Epub 2020 Jul 8.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.

Acetohydroxyacid synthase (AHAS), also known as acetolactate synthase, is a FAD and ThDP-Mg-dependent enzyme that catalyses the first step in the biosynthesis of the branched chain amino acids (BCAAs). It is the target for over 50 commercial herbicides. AHAS requires both catalytic and regulatory subunits for maximal activity and functionality. Read More

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http://dx.doi.org/10.1038/s41586-020-2514-3DOI Listing

Constitutional Thinness: tALKing the tALK or wALKing the wALK?

Cell Metab 2020 Jul;32(1):8-10

MRC Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK; Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK; Cambridge NIHR Biomedical Research Centre, Cambridge, UK; Addenbrooke's Hospital, Cambridge, UK. Electronic address:

In a recent issue of Cell, Orthofer et al. (2020) present a body of data from mice, flies, and humans that suggest (1) a physiological role for Alk in the normal control of energy balance across several species and (2) a possible contribution of genetic variants in or near ALK to the variability of adiposity in humans, more specifically at its lower end. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.012DOI Listing

Finding the Sweet Spot: Parsing Tissue-Specific Contributions of Fructose Metabolism.

Cell Metab 2020 Jul;32(1):6-8

Internal Medicine Research Unit, Pfizer Worldwide Research, Discovery and Medical, Cambridge, MA, USA. Electronic address:

The abundance of dietary sweeteners and overconsumption of fructose are widely thought to promote metabolic disease. In this issue of Cell Metabolism, Andres-Hernando et al. (2020) identify the liver as the major site of fructose metabolism-mediated metabolic dysfunction and identify a surprising role for intestinal fructose metabolism in driving fructose intake. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.009DOI Listing

Single-Cell and Population Transcriptomics Reveal Pan-epithelial Remodeling in Type 2-High Asthma.

Cell Rep 2020 Jul;32(1):107872

Center for Genes, Environment, and Health, National Jewish Health, Denver, CO 80206, USA; Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado-AMC, Aurora, CO 80045, USA. Electronic address:

The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To further investigate this incompletely understood pathobiology, we characterize IL-13 effects on human airway epithelial cell cultures using single-cell RNA sequencing, finding that IL-13 generates a distinctive transcriptional state for each cell type. Specifically, we discover a mucus secretory program induced by IL-13 in all cell types which converts both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. Read More

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http://dx.doi.org/10.1016/j.celrep.2020.107872DOI Listing

GM-CSF Calibrates Macrophage Defense and Wound Healing Programs during Intestinal Infection and Inflammation.

Cell Rep 2020 Jul;32(1):107857

Molecular Immunity Unit, University of Cambridge Department of Medicine, MRC Laboratory of Molecular Biology, Cambridge, UK; Wellcome Sanger Institute, Hinxton, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK. Electronic address:

Macrophages play a central role in intestinal immunity, but inappropriate macrophage activation is associated with inflammatory bowel disease (IBD). Here, we identify granulocyte-macrophage colony stimulating factor (GM-CSF) as a critical regulator of intestinal macrophage activation in patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis. We find that GM-CSF drives the maturation and polarization of inflammatory intestinal macrophages, promoting anti-microbial functions while suppressing wound-healing transcriptional programs. Read More

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http://dx.doi.org/10.1016/j.celrep.2020.107857DOI Listing

Tracing the Origin of Fibroblasts in Pancreatic Cancer.

Authors:
Giulia Biffi

Cell Mol Gastroenterol Hepatol 2020 Jul 5. Epub 2020 Jul 5.

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.jcmgh.2020.06.008DOI Listing

Toward an Individualized Neural Assessment of Receptive Language in Children.

J Speech Lang Hear Res 2020 Jul 8:1-25. Epub 2020 Jul 8.

Perception in Action Research Centre, Macquarie University, Sydney, New South Wales, Australia.

Purpose We aimed to develop a noninvasive neural test of language comprehension to use with nonspeaking children for whom standard behavioral testing is unreliable (e.g., minimally verbal autism). Read More

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http://dx.doi.org/10.1044/2020_JSLHR-19-00313DOI Listing

Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for ALS.

N Engl J Med 2020 07;383(2):109-119

From the Washington University School of Medicine, St. Louis (T.M., R.C.B., A.P.); the Healey Center for ALS, Massachusetts General Hospital, Harvard Medical School, Boston (M.C., N.A.), and Biogen, Cambridge (A.S., H.R., D.G., H.H., A.M., I.N., I.C., L.F., S.F., T.A.F.) - both in Massachusetts; the Sheffield Institute for Translational Neuroscience, University of Sheffield, and NIHR Sheffield Biomedical Research Centre and Clinical Research Facility, University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield (P.J.S., C.J.M.), and Biogen, Maidenhead (M.M.) - both in the United Kingdom; the Department of Clinical Science, Neurosciences, Umeå University, Umea, Sweden (P.M.A.); Montreal Neurological Institute and Hospital, Montreal (A.G.), and Sunnybrook Research Institute, Toronto (L.Z.); Emory University, Atlanta (J.G.); Barrow Neurological Institute, Phoenix, AZ (S.L.); the University of Ulm, Ulm, Germany (A.L.L.); Johns Hopkins University School of Medicine, Baltimore (N.J.M.); the University of California San Diego, La Jolla (J.R.), and Ionis Pharmaceuticals, Carlsbad (C.F.B., R.L.) - both in California; Paris ALS Centre, Hôpital de la Salpêtrière, Paris (F.S.); the University of Tennessee Medical Center, Knoxville (R.T.); and KU Leuven, VIB Center for Brain and Disease Research, University Hospitals Leuven, Leuven, Belgium (P.V.D.).

Background: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to mutations.

Methods: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to mutations. Read More

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http://dx.doi.org/10.1056/NEJMoa2003715DOI Listing

Social Prescribing - Transforming the Relationship between Physicians and Their Patients.

N Engl J Med 2020 Jul;383(2):97-99

From the University of Cambridge, Cambridge (M.R.), and the Bromley by Bow Health Centre (S.E.) and the Royal College of General Practitioners (M.M.), London - all in the United Kingdom.

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http://dx.doi.org/10.1056/NEJMp1917060DOI Listing

Impact of Oxidation Processes on the Composition and Biodegradability of Soluble Organic Nutrients in Wastewater Effluents.

Water Environ Res 2020 Jul 8. Epub 2020 Jul 8.

Cornell University, Ithaca, New York, United States.

The characteristics and bioavailability of wastewater derived organic nutrients and their susceptibility to removal technologies have implications in nutrient loading to aquatic environments and their contributions to eutrophication. Therefore, a better understanding of treatability of effluent organic nutrients is of interest for water resource recovery facilities (WRRFs) and regulators. Oxidation processes (OPs) can reduce concentrations of soluble organic nutrients and converting them into more biodegradable forms. Read More

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http://dx.doi.org/10.1002/wer.1393DOI Listing

Primary Pneumococcal Peritonitis can be the first presentation of a familial complement factor I deficiency.

Clin Exp Immunol 2020 Jul 8. Epub 2020 Jul 8.

Department of Infectious Diseases, Cambridge University Hospital NHS Trust, Cambridge, UK.

Primary pneumococcal peritonitis is a rare infection that has been described in women but has not been previously linked with immunodeficiency. The complement system plays a central role in immune defense against Streptococcus pneumoniae and, in order to evade complement attack, pneumococci have evolved a large number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis.We investigated an apparently immunocompetent woman with primary pneumococcal peritonitis and identified a family with deficiency for complement factor I. Read More

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http://dx.doi.org/10.1111/cei.13490DOI Listing

On holes and strings: Earliest displays of human adornment in the Middle Palaeolithic.

PLoS One 2020 8;15(7):e0234924. Epub 2020 Jul 8.

Zinman Institute of Archaeology, University of Haifa, Haifa, Israel.

Glycymeris shell beads found in Middle Palaeolithic sites are understood to be artifacts collected by modern humans for symbolic use. In Misliya Cave, Israel, dated to 240-160 ka BP, Glycymeris shells were found that were neither perforated nor manipulated; nevertheless, transportation to the cave is regarded as symbolic. In about 120 ka BP at Qafzeh Cave, Israel, modern humans collected naturally perforated Glycymeris shells also for symbolic use. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234924PLOS

Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in the JAK3 gene.

PLoS One 2020 8;15(7):e0235766. Epub 2020 Jul 8.

Division of Molecular Carcinogenesis, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235766PLOS

Criterion for Fingering Instabilities in Colloidal Gels.

Phys Rev Lett 2020 Jun;124(24):248006

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

We sandwich a colloidal gel between two parallel plates and induce a radial flow by lifting the upper plate at a constant velocity. Two distinct scenarios result from such a tensile test: (i) stable flows during which the gel undergoes a tensile deformation without yielding, and (ii) unstable flows characterized by the radial growth of air fingers into the gel. We show that the unstable regime occurs beyond a critical energy input, independent of the gel's macroscopic yield stress. Read More

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http://dx.doi.org/10.1103/PhysRevLett.124.248006DOI Listing

Stealth Entropy Production in Active Field Theories near Ising Critical Points.

Phys Rev Lett 2020 Jun;124(24):240604

DAMTP, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, United Kingdom.

We address the steady-state entropy production rate (EPR) of active scalar ϕ^{4} theories, which lack time-reversal symmetry, close to a phase-separation critical point. We consider both nonconserved (model A) and conserved (model B) dynamics at Gaussian level, and also address the former at leading order in ε=4-d. In each case, activity is irrelevant in the RG sense: the active model lies in the same (dynamic Ising) universality class as its time-reversible counterpart. Read More

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http://dx.doi.org/10.1103/PhysRevLett.124.240604DOI Listing

Zhao et al. Reply.

Phys Rev Lett 2020 Jun;124(24):249702

Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.

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http://dx.doi.org/10.1103/PhysRevLett.124.249702DOI Listing

Self-Excited Motions of Volatile Drops on Swellable Sheets.

Phys Rev Lett 2020 Jun;124(25):258002

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.

When a volatile droplet is deposited on a floating swellable sheet, it becomes asymmetric, lobed and mobile. We describe and quantify this phenomena that involves nonequilibrium swelling, evaporation and motion, working together to realize a self-excitable spatially extended oscillator. Solvent penetration causes the film to swell locally and eventually buckle, changing its shape and the drop responds by moving. Read More

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http://dx.doi.org/10.1103/PhysRevLett.124.258002DOI Listing

Forming a Single Molecule by Magnetoassociation in an Optical Tweezer.

Phys Rev Lett 2020 Jun;124(25):253401

Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA.

We demonstrate the formation of a single NaCs molecule in an optical tweezer by magnetoassociation through an s-wave Feshbach resonance at 864.11(5) G. Starting from single atoms cooled to their motional ground states, we achieve conversion efficiencies of 47(1)%, and measure a molecular lifetime of 4. Read More

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http://dx.doi.org/10.1103/PhysRevLett.124.253401DOI Listing

Dynamo in Weakly Collisional Nonmagnetized Plasmas Impeded by Landau Damping of Magnetic Fields.

Phys Rev Lett 2020 Jun;124(25):255102

Department of Physics, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.

We perform fully kinetic simulations of flows known to produce dynamo in magnetohydrodynamics (MHD), considering scenarios with low Reynolds number and high magnetic Prandtl number, relevant for galaxy cluster scale fluctuation dynamos. We find that Landau damping on the electrons leads to a rapid decay of magnetic perturbations, impeding the dynamo. This collisionless damping process operates on spatial scales where electrons are nonmagnetized, reducing the range of scales where the magnetic field grows in high magnetic Prandtl number fluctuation dynamos. Read More

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http://dx.doi.org/10.1103/PhysRevLett.124.255102DOI Listing

Correction: 3D aggregation of cells in packed microgel media.

Soft Matter 2020 Jul 8. Epub 2020 Jul 8.

Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA and Department of Materials Science and Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA and J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.

Correction for '3D aggregation of cells in packed microgel media' by Cameron D. Morley et al., Soft Matter, 2020, DOI: 10. Read More

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http://dx.doi.org/10.1039/d0sm90130jDOI Listing

Autologous versus Implant-Based Reconstruction: Long-Term Costs and Health Care Use.

Plast Reconstr Surg 2020 Jun 29. Epub 2020 Jun 29.

Kellogg College, University of Oxford, UK.

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http://dx.doi.org/10.1097/PRS.0000000000007176DOI Listing

COVID-19 preparedness and response at a large UK major trauma operating theatres department.

J Perioper Pract 2020 Jul;30(7-8):210-220

Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Perioperative Care Services, Cambridge, UK.

This article aims to describe the early experience of a large major trauma operating theatres department in the East of England during the outbreak of the coronavirus disease 2019 (COVID-19) pandemic. To date and to our knowledge, a small amount of reports describing a surgical department's response to this unprecedented pandemic have been published, but a well-documented account from within the United Kingdom (UK) has not yet been reported in the literature. We describe our preparation and response, including: operating theatres management during the COVID-19 pandemic, operational aspects and communication, leadership and support. Read More

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http://dx.doi.org/10.1177/1750458920934406DOI Listing

Fractional viscoelastic models for power-law materials.

Soft Matter 2020 Jul;16(26):6002-6020

Department of Engineering, University of Cambridge, UK.

Soft materials often exhibit a distinctive power-law viscoelastic response arising from broad distribution of time-scales present in their complex internal structure. A promising tool to accurately describe the rheological behaviour of soft materials is fractional calculus. However, its use in the scientific community remains limited due to the unusual notation and non-trivial properties of fractional operators. Read More

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http://dx.doi.org/10.1039/d0sm00354aDOI Listing

Statistical Power and the Classical Twin Design.

Twin Res Hum Genet 2020 Apr;23(2):87-89

Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.

Dr Nick Martin has made enormous contributions to the field of behavior genetics over the past 50 years. Of his many seminal papers that have had a profound impact, we focus on his early work on the power of twin studies. He was among the first to recognize the importance of sample size calculation before conducting a study to ensure sufficient power to detect the effects of interest. Read More

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http://dx.doi.org/10.1017/thg.2020.46DOI Listing

Rates of delirium associated with calcium channel blockers compared to diuretics, renin-angiotensin system agents and beta-blockers: An electronic health records network study.

J Psychopharmacol 2020 Jul 8:269881120936501. Epub 2020 Jul 8.

Department of Psychiatry, University of Oxford, Oxford, UK.

Background: Antihypertensive drugs, especially calcium channel blockers, have been associated with differential rates of a number of neuropsychiatric outcomes. Delirium is commonly attributed to medication, including antihypertensive drugs, but delirium incidence has not been compared directly between antihypertensive drug classes.

Methods: Using a federated electronic health records network of 25. Read More

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http://dx.doi.org/10.1177/0269881120936501DOI Listing

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

Colorectal Dis 2020 Jul 7. Epub 2020 Jul 7.

Department of Surgery, SSORG - Scandinavian Surgical Outcomes Research Group, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Aim: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons.

Methods: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Read More

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http://dx.doi.org/10.1111/codi.15140DOI Listing

Can high school students save Teddy Bear Hospital?

Clin Teach 2020 Jul 8. Epub 2020 Jul 8.

School of Clinical Medicine, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1111/tct.13206DOI Listing

Tuning into the real effect of smartphone use on parenting: a multiverse analysis.

J Child Psychol Psychiatry 2020 Jul 7. Epub 2020 Jul 7.

Science Unit, Australian Broadcasting Corporation (ABC), Sydney, NSW, Australia.

Background: Concerns have been raised regarding the potential negative impacts of parents' smartphone use on the parent-child relationship. A scoping literature review indicated inconsistent effects, arguably attributable to different conceptualizations of parent phone use and conflation of phone use with technological interference.

Methods: Based on a sample of n = 3, 659 parents collected in partnership with a national public broadcaster, we conducted a multiverse analysis. Read More

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http://dx.doi.org/10.1111/jcpp.13282DOI Listing

A prospective study of erythrocyte polyunsaturated fatty acids and risk of colorectal serrated polyps and conventional adenomas.

Int J Cancer 2020 Jul 7. Epub 2020 Jul 7.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

The influence of polyunsaturated fatty acids (PUFAs) on risk of colorectal cancer precursors remains largely unknown. We examined the associations of erythrocyte PUFAs, including n-3 and n-6 PUFAs, with risk of colorectal conventional adenomas and serrated polyps in 4517 participants from three U.S. Read More

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http://dx.doi.org/10.1002/ijc.33190DOI Listing

Impact of COVID-19 on U.S. and Canadian neurologists' therapeutic approach to multiple sclerosis: a survey of knowledge, attitudes, and practices.

J Neurol 2020 Jul 7. Epub 2020 Jul 7.

Department of Neurology, Massachusetts General Hospital, 165 Cambridge Street, Office 627, Boston, MA, 02114, USA.

Objective: To report the understanding and decision-making of neuroimmunologists and their treatment of patients with multiple sclerosis (MS) during the early stages of the SARS-CoV-2 (COVID-19) outbreak.

Methods: A survey instrument was designed and distributed online to neurologists in April 2020.

Results: There were 250 respondents (response rate 21. Read More

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http://dx.doi.org/10.1007/s00415-020-10045-9DOI Listing

Neurological update: neuroimaging in dementia.

Authors:
Timothy Rittman

J Neurol 2020 Jul 7. Epub 2020 Jul 7.

Department of Neurosciences, University of Cambridge, Cambridge, UK.

Neuroimaging for dementia has made remarkable progress in recent years, shedding light on diagnostic subtypes of dementia, predicting prognosis and monitoring pathology. This review covers some updates in the understanding of dementia using structural imaging, positron emission tomography (PET), structural and functional connectivity, and using big data and artificial intelligence. Progress with neuroimaging methods allows neuropathology to be examined in vivo, providing a suite of biomarkers for understanding neurodegeneration and for application in clinical trials. Read More

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http://dx.doi.org/10.1007/s00415-020-10040-0DOI Listing

Clinical validation of the novel HDAC6 radiotracer [F]EKZ-001 in the human brain.

Eur J Nucl Med Mol Imaging 2020 Jul 8. Epub 2020 Jul 8.

Eikonizo Therapeutics, Inc., LabCentral, 700 Main Street North, Cambridge, MA, 02139, USA.

Purpose: Histone deacetylase 6 (HDAC6) is a cytoplasmic enzyme that modulates intracellular transport and protein quality control. Inhibition of HDAC6 deacetylase activity has shown beneficial effects in disease models, including Alzheimer's disease and amyotrophic lateral sclerosis. This first-in-human positron emission tomography (PET) study evaluated the brain binding of [F]EKZ-001 ([F]Bavarostat), a radiotracer selective for HDAC6, in healthy adult subjects. Read More

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http://dx.doi.org/10.1007/s00259-020-04891-yDOI Listing

The effects of acute serotonin challenge on executive planning in patients with obsessive-compulsive disorder (OCD), their first-degree relatives, and healthy controls.

Psychopharmacology (Berl) 2020 Jul 8. Epub 2020 Jul 8.

SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Rationale: Obsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. Read More

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http://dx.doi.org/10.1007/s00213-020-05597-7DOI Listing

Hallucinations in Older Adults: A Practical Review.

Schizophr Bull 2020 Jul 8. Epub 2020 Jul 8.

Rijks Universiteit Groningen (RUG), Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, The Netherlands.

Older adults experience hallucinations in a variety of social, physical, and mental health contexts. Not everyone is open about these experiences, as hallucinations are surrounded with stigma. Hence, hallucinatory experiences in older individuals are often under-recognized. Read More

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http://dx.doi.org/10.1093/schbul/sbaa073DOI Listing

Iceland is an episodic source of atmospheric ice-nucleating particles relevant for mixed-phase clouds.

Sci Adv 2020 Jun 24;6(26):eaba8137. Epub 2020 Jun 24.

School of Earth and Environment, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK.

Ice-nucleating particles (INPs) have the potential to remove much of the liquid water in climatically important mid- to high-latitude shallow supercooled clouds, markedly reducing their albedo. The INP sources at these latitudes are very poorly defined, but it is known that there are substantial dust sources across the high latitudes, such as Iceland. Here, we show that Icelandic dust emissions are sporadically an important source of INPs at mid to high latitudes by combining ice-nucleating active site density measurements of aircraft-collected Icelandic dust samples with a global aerosol model. Read More

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http://dx.doi.org/10.1126/sciadv.aba8137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314534PMC

Capacitance of thin films containing polymerized ionic liquids.

Sci Adv 2020 Jun 26;6(26):eaba7952. Epub 2020 Jun 26.

Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.

Electrode-polymer interfaces dictate many of the properties of thin films such as capacitance, the electric field experienced by polymers, and charge transport. However, structure and dynamics of charged polymers near electrodes remain poorly understood, especially in the high concentration limit representative of the melts. To develop an understanding of electric field-induced transformations of electrode-polymer interfaces, we have studied electrified interfaces of an imidazolium-based polymerized ionic liquid (PolyIL) using combinations of broadband dielectric spectroscopy, specular neutron reflectivity, and simulations based on the Rayleigh's dissipation function formalism. Read More

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http://dx.doi.org/10.1126/sciadv.aba7952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319767PMC

Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal.

Sci Adv 2020 Jun 26;6(26):eaba4353. Epub 2020 Jun 26.

Department of Medicine, Altman Clinical and Translational Research Institute, University of California, San Diego, La Jolla, CA 92093, USA.

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Read More

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http://dx.doi.org/10.1126/sciadv.aba4353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319753PMC

Impact of mRNA chemistry and manufacturing process on innate immune activation.

Sci Adv 2020 Jun 24;6(26):eaaz6893. Epub 2020 Jun 24.

Moderna Inc., 200 Technology Square, Cambridge, MA, USA.

Messenger RNA (mRNA) represents an attractive therapeutic modality for potentially a wide range of clinical indications but requires uridine chemistry modification and/or tuning of the production process to prevent activation of cellular innate immune sensors and a concomitant reduction in protein expression. To decipher the relative contributions of these factors on immune activation, here, we compared, in multiple cell and in vivo models, mRNA that encodes human erythropoietin incorporating either canonical uridine or 1-methyl-pseudouridine (1mΨ), synthesized by either a standard process shown to have double-stranded RNA (dsRNA) impurities or a modified process that yields a highly purified mRNA preparation. Our data demonstrate that the lowest stimulation of immune endpoints was with 1mΨ made by the modified process, while mRNA containing canonical uridine was immunostimulatory regardless of process. Read More

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http://dx.doi.org/10.1126/sciadv.aaz6893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314518PMC

Recursive sequence generation in monkeys, children, U.S. adults, and native Amazonians.

Sci Adv 2020 Jun 26;6(26):eaaz1002. Epub 2020 Jun 26.

Carnegie Mellon University, Pittsburgh, PA, USA.

The question of what computational capacities, if any, differ between humans and nonhuman animals has been at the core of foundational debates in cognitive psychology, anthropology, linguistics, and animal behavior. The capacity to form nested hierarchical representations is hypothesized to be essential to uniquely human thought, but its origins in evolution, development, and culture are controversial. We used a nonlinguistic sequence generation task to test whether subjects generalize sequential groupings of items to a center-embedded, recursive structure. Read More

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http://dx.doi.org/10.1126/sciadv.aaz1002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319756PMC

Diagnosis of a Lymphoenteric Fistula by Single-Photon Emission Computed Tomography/Computed Tomography Lymphoscintigraphy.

ACG Case Rep J 2020 Jun 11;7(6):e00388. Epub 2020 Jun 11.

Department of Allergy and Clinical Immunology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.

Protein losing enteropathy can present as an immunodeficiency. This report describes a rare cause of protein losing enteropathy due to a lymphoenteric fistula and how a novel use of a pre-existing combined imaging technique of single-photon emission computed tomography/computed tomography lymphoscintigraphy helped in making the diagnosis. Read More

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http://dx.doi.org/10.14309/crj.0000000000000388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304535PMC

Characterization of continuous wave ultrasound for acousto-optic modulated diffuse correlation spectroscopy (AOM-DCS).

Biomed Opt Express 2020 Jun 14;11(6):3071-3090. Epub 2020 May 14.

Optics at Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

Intra and post-operative blood flow monitoring of tissue has been shown to be effective in the improvement of patient outcomes. Diffuse correlation spectroscopy (DCS) has been shown to be effective in measuring blood flow at the bedside, and is a useful technique in measuring cerebral blood flow (CBF) in many clinical settings. However, DCS suffers from reduced sensitivity to blood flow changes at larger tissue depths, making measurements of CBF in adults difficult. Read More

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http://dx.doi.org/10.1364/BOE.390322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316011PMC

A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes.

Bone Res 2020 1;8:26. Epub 2020 Jul 1.

Department of Hygiene and Epidemiology, Clinical and Molecular Epidemiology Unit, School of Medicine, University of Ioannina, Ioannina, Greece.

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration. Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype. We aimed to identify pleiotropic loci associated with bone mineral density (BMD) and nonbone phenotypes in genome-wide association studies. Read More

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http://dx.doi.org/10.1038/s41413-020-0101-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329904PMC

Preservation of erniettomorph fossils in clay-rich siliciclastic deposits from the Ediacaran Wood Canyon Formation, Nevada.

Interface Focus 2020 Aug 12;10(4):20200012. Epub 2020 Jun 12.

Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, USA.

Three-dimensionally preserved Ediacaran fossils occur globally within sandstone beds. Sandy siliciclastic deposits of the Ediacaran Wood Canyon Formation (WCF) in the Montgomery Mountains, Nevada, contain two fossil morphologies with similar shapes and sizes: one exhibits mm-scale ridges and a distinct lower boundary and the other is devoid of these diagnostic features. We interpret these as taphomorphs of erniettomorphs, soft-bodied organisms with uncertain taxonomic affinities. Read More

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http://dx.doi.org/10.1098/rsfs.2020.0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333903PMC

Fifteen Years of Sm-p80-Based Vaccine Trials in Nonhuman Primates: Antibodies From Vaccinated Baboons Confer Protection and From and Identification of Putative Correlative Markers of Protection.

Front Immunol 2020 19;11:1246. Epub 2020 Jun 19.

Center for Tropical Medicine and Infectious Diseases, Texas Tech University Health Sciences Center, Lubbock, TX, United States.

Recent advances in systems biology have shifted vaccine development from a largely trial-and-error approach to an approach that promote rational design through the search for immune signatures and predictive correlates of protection. These advances will doubtlessly accelerate the development of a vaccine for schistosomiasis, a neglected tropical disease that currently affects over 250 million people. For over 15 years and with contributions of over 120 people, we have endeavored to test and optimize Sm-p80-based vaccines in the non-human primate model of schistosomiasis. Read More

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http://dx.doi.org/10.3389/fimmu.2020.01246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318103PMC

Genome-Scale Metabolic Model Driven Design of a Defined Medium for M1cam.

Front Microbiol 2020 19;11:1072. Epub 2020 Jun 19.

Microbes in Food Chain, Quadram Institute Biosciences, Norwich Research Park, Norwich, United Kingdom.

, the most frequent cause of food-borne bacterial gastroenteritis, is a fastidious organism when grown in the laboratory. Oxygen is required for growth, despite the presence of the metabolic mechanism for anaerobic respiration. Amino acid auxotrophies are variably reported and energy metabolism can occur through several electron donor/acceptor combinations. Read More

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http://dx.doi.org/10.3389/fmicb.2020.01072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318876PMC

Constraints on terrestrial planet formation timescales and equilibration processes in the Grand Tack scenario from Hf-W isotopic evolution.

Earth Planet Sci Lett 2019 Sep 16;522:210-218. Epub 2019 Jul 16.

Northwestern University, Dept. Earth and Planetary Sciences, 2145 Sheridan Road, Evanston, IL 60208, USA.

We examine 141 N-body simulations of terrestrial planet late-stage accretion that use the Grand Tack scenario, coupling the collisional results with a hafnium-tungsten (Hf-W) isotopic evolution model. Accretion in the Grand Tack scenario results in faster planet formation than classical accretion models because of higher planetesimal surface density induced by a migrating Jupiter. Planetary embryos which grow rapidly experience radiogenic ingrowth of mantle tungsten which is inconsistent with the measured terrestrial value, unless much of the tungsten is removed by an impactor core that mixes thoroughly with the target mantle. Read More

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http://dx.doi.org/10.1016/j.epsl.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339907PMC
September 2019

Advances toward precision medicine for bipolar disorder: mechanisms & molecules.

Mol Psychiatry 2020 Jul 7. Epub 2020 Jul 7.

Center for Quantitative Health, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Given its chronicity, contribution to disability and morbidity, and prevalence of more than 2%, the effective treatment, and prevention of bipolar disorder represents an area of significant unmet medical need. While more than half a century has passed since the introduction of lithium into widespread use at the birth of modern psychopharmacology, that medication remains a mainstay for the acute treatment and prevention of recurrent mania/hypomania and depression that characterize bipolar disorder. However, the continued limited understanding of how lithium modulates affective behavior and lack of validated cellular and animal models have resulted in obstacles to discovering more effective mood stabilizers with fewer adverse side effects. Read More

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http://dx.doi.org/10.1038/s41380-020-0831-4DOI Listing

Author Correction: Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study.

Sci Rep 2020 Jul 7;10(1):11160. Epub 2020 Jul 7.

Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

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http://dx.doi.org/10.1038/s41598-020-68532-yDOI Listing

The VIP-VPAC2 neuropeptidergic axis is a cellular pacemaking hub of the suprachiasmatic nucleus circadian circuit.

Nat Commun 2020 Jul 7;11(1):3394. Epub 2020 Jul 7.

MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus, Cambridge, CB2 0QH, UK.

The hypothalamic suprachiasmatic nuclei (SCN) are the principal mammalian circadian timekeeper, co-ordinating organism-wide daily and seasonal rhythms. To achieve this, cell-autonomous circadian timing by the ~20,000 SCN cells is welded into a tight circuit-wide ensemble oscillation. This creates essential, network-level emergent properties of precise, high-amplitude oscillation with tightly defined ensemble period and phase. Read More

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http://dx.doi.org/10.1038/s41467-020-17110-xDOI Listing